We will continue studies on the lymphatic system to determine the initial development of the lymphatic sacs (jugular, retroperitoneal and posterior) and the role of pulmonary lymphatics in the removal of fluids, large molecules and particulate substances from the interstitium in the normal lung and in pulmonary edema. The development of the lymphatic system will be investigated in the fetuses of mice beginning at day nine (9) of gestation up to birth at day twenty one (21). The initial development of the lymphatic system and the manner in which the various anlagen (lymphatic sacs) are formed and become interconnected will be investigated in normal mice using the combined techniques of histology, transmission and scanning electron microscopy, cytochemistry and high voltage electron microscopy. Pulmonary edema is characterized by the presence of excessive amounts of water and plasma proteins within the interstitium, air space or cells of the lung. We will examine the pulmonary microvascular bed surrounding the pulmonary alveolus in the normal and the edematous lungs to determine the sites of increased permeability of the endothelium. We will also determine the pathways for the movement and distribution of large molecules and cells from the pulmonary microvascular bed into the interstitium and subsequent removal by pulmonary lymphatics. To accomplish these goals, we will collaborate with Dr. LaVal Cothran of the Department of Physiology and Biophysics and the Cardiovascular Research Laboratory of Howard University who will provide animal models (hypertensive dogs) that will be used for the pulmonary edema studies outlined in this proposal. The lungs from these animals will be examined using combined methods of histology, cytochemistry, physiological methods, transmission and scanning electron microscopy, backscatter electron imaging and freeze fracture replication.